The goal of this project it to better understand the natural history of Lyme disease and possible causes for persisting symptoms. We plan to develop reliable objective markers of infection, of clinical status and of host responses to the organism in order to discern the scope and the implications of persistent borrelial infection, the effectiveness of current treatment options, and the development of new therapeutics approaches. For that, a clinical protocol was developed and approved by the NIAID IRB. The study is assembling a well characterized cohort of patients with presumed chronic Lyme disease and relevant controls. These patients are being extensively evaluated in a cross-sectional study and the neuroborreliosis patients will be followed prospectively after therapy with intervenous ceftriaxone. These studies will yield a prospective database upon which stringent diagnostic criteria can be established and future therapeutic trials can be designed. At this point, 18 patients have been enrolled in the study. This study is in its early phase of development, and, at this point, it is too early to draw conclusions from the analysis of the results of the multiple and extensive testing done in the enrolled patients